Sie sind auf Seite 1von 19

Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve...

Pagina 1 di 19

Mens Sana Monogr. 2010 Jan–Dec; 8(1): 53–68. PMCID: PMC3031940


doi: 10.4103/0973-1229.58819.

Copyright © Mens Sana Monographs

Weight-Gain in Psychiatric Treatment: Risks, Implications, and


Strategies for Prevention and Management
Amresh Shrivastava* and Megan E. Johnston**
*The University of Western Ontario, Department of Psychiatry, & Associate Scientist, Lawson health Research Institute,

London, ON, Canada


**University of Toronto, Department of Psychology, Toronto, ON, Canada

Address correspondence to: Dr. Amresh Shrivastava, Regional Mental Health Care, 467 Sunset Drive, St.Thomas, ON,
Canada. N5H 3V9. E-mail: dr.amresh@gmail.com

Received October 3, 2009; Revised December 23, 2009; Accepted December 24, 2009.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Weight-gain in psychiatric populations is a common clinical challenge. Many patients


suffering from mental disorders, when exposed to psychotropic medications, gain
significant weight with or without other side-effects. In addition to reducing the patients’
willingness to comply with treatment, this weight-gain may create added psychological or
physiological problems that need to be addressed. Thus, it is critical that clinicians take
precautions to monitor and control weight-gain and take into account and treat all
problems facing an individual. In this review, we examine some of the key issues
surrounding weight-gain in individuals suffering from mental disorders for contemporary
practitioners in community clinics. We describe some factors known to make certain
patients more susceptible to treatment-induced weight-gain and mechanisms implicated
in this process. We also highlight a few psychological and pharmacological interventions
that have proven effective in weight management. Importantly, we provide critical steps
for management and prevention of weight-gain and related issues in the clinical practice
of psychopharmacology.
Keywords: Weight gain, psychiatric patients, antipsychotics, antidepressants, treatment-
induced weight-gain, psychopharmacology

Introduction

Weight-gain in psychiatric populations is a common clinical challenge. Many patients


suffering from mental disorders, when exposed to psychotropic medications, gain

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 2 di 19

significant weight with or without other side effects. Being overweight or obese has been
acknowledged as a public health problem due to its correlation with mortality and
increased comorbidity of other physical disorders. This association requires new
paradigms of management of psychiatric disorders that take into account comorbid
physical disorders.

When treated over a short period of time, weight-gain may be minimal and reversible
once a drug is discontinued. With long-term treatment, however, psychiatric patients may
gain a significant amount of weight, possibly reducing their willingness to comply with
treatment. Additionally, this weight-gain may create added psychological or physiological
problems that need to be addressed. Thus, it is critical that clinicians take precautions to
monitor and control weight-gain to take into account and treat all problems facing such
an individual.

In this review, we examine some of the key issues surrounding weight-gain in individuals
suffering from mental disorders for contemporary practitioners in community clinics. We
discuss measures that can be adopted in practice to deal with this issue while optimizing
treatment and outcome. We start by providing an overview for practicing clinicians on the
evidence and course of weight-gain during psychiatric treatment and some of the issues
this entails. We describe some factors known to make certain patients more susceptible
to treatment-induced weight-gain and mechanisms implicated in this process. Finally, we
provide critical steps for management and prevention of weight-gain and related issues
in the clinical practice of psychopharmacology.

Evidence of Weight-gain

The prevalence of obesity is increasing at an alarming rate. This has led to an increase
in research into the causes, comorbidities, and treatment of obesity in recent years.
Clinical studies indicate that a high prevalence of metabolic syndrome exists in
individuals afflicted with serious mental illnesses, particularly those with schizophrenia. In
addition, psychotropic agents, including antipsychotic medications and antidepressants,
have been found to be associated with substantial weight-gain (Newcomer, 2007). This
weight-gain is troublesome as it increases an individual’s risk of diabetes and
cardiovascular disease. A normal body mass index (BMI) is considered to be between
18.5 and 24.9, a BMI between 25 and 29.9 is classified as overweight, and 30 to 39.9
denotes obesity. Patients with a BMI above 40 are considered extremely obese (Morrato,
2009)

Research examining the differential effects of various antipsychotic medications has


shown that both the frequency as well as the amount of weight-gained is high in patients
treated with olanzapine (average gain of 2.3 kg/month), clozapine (1.7 kg/month),

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 3 di 19

quetiapine (1.8 kg/month), and zotepine (2.3 kg/month), (Wetterling, 2001). Additionally,
they also report that some changes in weight have also been observed in treatment with
risperidone (average gain of 1.0 kg/month), and ziprasidone seems to induce only small
changes in weight (0.8 kg/month). Overall, the largest body of research exists to support
an association between weight-gain and treatment with olazapine and clozapine
(Gebhardt et al. 2009; Haddad, 2005).

The strength of the causal relationship between antipsychotic drug exposure and weight-
gain can be assessed using a drugs trial conducted with antipsychotic-naive patients.
Tarricone and colleagues (2009) reviewed 11 studies reporting the effects of
antipsychotic drugs on body weight in patients naïve to antipsychotic drugs. The mean
values of weight-gain in these patients were highly significant from the first few weeks of
treatment. The sample averaged around 3.8 kg in gained weight and an increase of 1.2
in body mass index (BMI). Thus, weight-gain associated with antipsychotic drug
treatment appears to occur rapidly in the first few weeks and continue during the
following months (Tarricone et al.. 2009).

Weight-gain is not restricted to individuals treated with antipsychotics; antidepressants


and lithium have also been shown to lead to unwanted weight-gain. Studies have found
that antidepressants lead to an increase of weight in anywhere between 24-100% of
patients, with an average weight-gain of 0.57 to 1.37 kg per month of treatment (Fava,
2000; Garland et al. 1988). Lithium carbonate therapy is also associated with significant
weight-gain, with some studies reporting a gain of over 10 kg in 20% of patients
(Livingstone& Rampes, 2006; Vestergaard et al. 1980).

It should be noted that not all psychotropic drugs lead to weight-gain, and some have
even been shown to decrease weight, such as serotonin-reuptake inhibitors (SSRI)
during the first few weeks of use (Michelson et al. 2000), felbamate (Bergen et al. 1995),
and topiramate (Dursun& Devarajan, 2000).

When does weight-gain occur?


In their sample of bipolar patients, Fagiolini et al. (2002) found that most weight-gain
occurred during acute treatment rather than during maintenance treatment. This
research demonstrated the benefit of maintenance treatment as minimal weight was
gained during the maintenance phase, whereas acute depressive episodes were related
to weight-gain. Also, stabilization on maintenance medication facilitates participation in
interventions directed specifically at weight loss (Fagiolini et al. 2002).

In patients treated with clozapine, Umbricht et al. (1994) found that significant weight-
gain occurred primarily during the first six to 12 months, and continued into the third year
of treatment. These researchers found that being underweight at baseline was correlated

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 4 di 19

with a greater amount of weight-gained, while overweight status at baseline was


associated with a higher final weight following treatment than those who were not
overweight at baseline.

Several long-term naturalistic studies found that weight-gain is less marked in the long
term than in controlled trials of a shorter or comparable duration. With the use of many
antipsychotics, weight may stabilize in the short to medium term but it appears that
weight-gain continues beyond the first year when treated with clozapine (Haddad, 2005).
Some predictors of long-term weight-gain include a lower body mass index, a rapid initial
increase in weight, and increased appetite. Weight-gain also seems to be greater in first
onset patients due to their lack of prior antipsychotic treatment and the weight-gain
associated with these treatments (Haddad, 2005). Fortunately, it does seem that weight-
gain resulting from antipsychotics occurs primarily during the first two years of treatment
and then levels off (Silverstone et al. 1988, Allison, 2009).

Is Weight-gain dose-dependent?
A recent review attempted to answer the question of whether weight-gain and associated
metabolic changes are dose-dependent (Simon et al. 2009). A relationship appears to
exist between the administered dose of clozapine and olanzapine and metabolic
outcomes. With regard to risperidone and other antipsychotic medications, further
research is required to make an accurate assessment of a possible dose-dependency for
weight-gain (Simon et al. 2009). However, the relationship between clozapine and
olanzapine plasma concentrations and metabolic disturbances provide evidence for a
causal effect of antipsychotic medications on weight-gain.

Clinical Impact of Weight-gain

Morbidity, mortality, and physical health


Research suggests that individuals with severe mental illness have significantly worse
health outcomes and premature mortality than the general population. Individuals with
schizophrenia have up to a 20% shorter lifespan compared to the general population,
with cardiovascular disease representing the most common cause of death (Newcomer,
2007). Many factors are implicated in the poor health of individuals with schizophrenia,
including increased prevalence of smoking, poverty, and poor nutrition (Newcomer,
2007); additional contributions are made by the adverse metabolic side effects of
antipsychotic medications, including weight-gain (Amiel et al. 2008). An important aspect
of managing mental illness is managing the side effects of antipsychotics using a
combination of administrative, behavioral and medical approaches (Amiel et al. 2008).

An additional issue is that overweight and obese individuals are at risk for numerous
psychological and physiological health problems, such as depression and disordered

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 5 di 19

eating (Bean et al. 2008). Hence, mental health professionals need to take special care
in the case of patients with obesity, to watch for and treat these additional health
concerns if they should arise. Evidence suggests that mentally ill patients often do not
receive adequate care for their medical illnesses, highlighting the need for increased
awareness of and attention to the physical health problems of individuals with mental
illness (Newcomer, 2007). In particular, the metabolic and weight issues resulting from
antipsychotic treatments require appropriate management.

Weight-gain in Specific Conditions

Affective disorders
Major depressive disorder can be a chronic condition involving recurrent episodes
throughout a patient’s life. In order to reduce the chance of relapse, long-term treatment
with antidepressants is necessary. Unfortunately, many patients choose to discontinue
medication due to long-term side effects resulting from these drugs, one of which is
weight-gain (Moller, 2008). In one group of individuals with bipolar disorder, Fagiolini and
colleagues (2002) found that 68% of the patients were obese or overweight at entry into
the study; 32% of the individuals in the study were classified as obese. Additionally, it
was found that the number of previous depressive episodes experienced by an individual
was associated with being overweight or obese at study entry (Fagiolini et al. 2002).
Thus, weight-gain seems especially prevalent in affective disorders, although this likely
results from both the effects of the illness as well as treatment effects. Clearly, in this
group of patients, weight management and control is particularly critical to include as part
of a treatment program.

Childhood and adolescence


The prevalence of pediatric obesity is rising in both developed and developing countries.
As overweight children and adolescents are at an increased risk of medical comorbidities
and psychosocial and behavioral difficulties, this makes antipsychotic-induced weight-
gain a significant public health concern (Jelalian et al. 2007). Children and adolescents
are known to be at a higher risk for weight-gain associated with antipsychotic treatment
(Citrome& Vreeland, 2009). A recent study looked at antipsychotic-induced weight-gain
in a pediatric sample and noted marked and rapid weight-gain (Correll et al. 2009).
Children and adolescents between the ages of 4 and 18 were treated with aripiprazole,
olanzapine, quetiapine, or risperidone for 12 weeks and results showed an average
weight-gain between 4.4 and 8.5 kg depending on the agent (highest gain was in
olanzapine patients, lowest gain in aripiprazole patients).

Many current pediatric weight control interventions proven to be effective in research


trials are limited by samples that may exclude participants with psychiatric co-morbidities
(Jelalian et al. 2007). Thus, it is important that clinicians treating overweight and obese

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 6 di 19

children and adolescents with psychiatric disorder assess individual, familial, and
contextual variables specific to weight in order to prioritize treatment objectives. Similar to
adults, weight-gain is an important consideration for practitioners treating children and
adolescents with antipsychotics especially, as the detrimental effects of weight-gain, both
psychological and physiological, may manifest to a greater degree in children. Future
research is needed to explore these issues.

Pregnancy
Many women with psychotic disorders have children at some point in their lives, leading
to a new set of issues. Women with schizophrenia receive less prenatal care and have
poorer health, resulting in many health risks for their infants (Howard, 2005). McKenna et
al. (2005) followed pregnant women taking atypical antipsychotics (olanzapine,
risperidone, quetiapine, and clozapine) and found a greater BMI in the mothers and lower
birth weight in the infants. Weight-gain and increased BMI pose many health risks for
pregnant women as obesity is associated with obstetric complications, including
gestational diabetes mellitus, pre-eclampsia, and caesarean delivery (Brost et al. 1997).
Obesity also poses a risk to the children they are carrying. Boney et al. (2005) found that
children exposed to maternal obesity in the womb were more likely to have metabolic
syndrome themselves, and pregnancies in obese women are more likely to result in
stillbirth and neonatal deaths than pregnancies in women of normal weight (Kristensen,
2005). Thus, weight-gain as a result of antipsychotic medication can pose additional risks
to women who are pregnant and may result in negative health consequences for these
mothers and their infants.

Dementia
Body mass index (BMI) may influence or be influenced by the brain structures and
functions involved in dementia processes (Gustafson, 2008). The adipose tissue
associated with BMI changes over the lifespan and is related to brain development in
terms of cognitive functioning, intelligence, and cognitive disorders such as dementia. In
general, lower BMIs and correspondingly greater rates of weight decline during the years
preceding dementia onset, are related to dementia. Risk of dementia is increased,
however, by a high BMI during mid-life or in the 5-10 years preceding dementia onset
(Gustafson, 2008)

Public Health

The weight-gain associated with antipsychotic medications represents a liability to the


public health system. A variety of factors make schizophrenia an economic burden on
society, including unemployment, incarceration, and healthcare (Goeree et al. 2005); but
obesity represents an additional factor adding to this burden. It may be more difficult to
treat obesity in individuals who have gained weight as a result of antipsychotic treatment

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 7 di 19

as their medication increases appetite and produces fatigue and the illness itself
decreases motivation and social activities (Centorrino et al. 2006). Thus, these
individuals who have gained weight as a result of their psychiatric treatment are an
additional cost to the healthcare system. The medical and health risks associated with
obesity result in a cost to society beyond that of psychiatric care alone.

Individual Susceptibility

Research using data from twin, adoption, and family studies suggests that at least 50%
of individual difference in body mass index (BMI) is due to genetic factors. However, the
increase in obesity rates over recent years illustrates the impact of environmental factors
on body weight (Hebebrand& Hinney, 2008). Males and females are also differentially
susceptible to weight-gain. Gender differences are apparent in how and where body fat
is stored, as men amass more fat in the intra-abdominal area than pre-menopausal
women. This increases males’ risk of developing cardiovascular problems, type-2
diabetes mellitus, certain cancers and other metabolic problems that relate to obesity
(Shi& Clegg, 2009).

The increased appetite, and associated weight-gain, resulting from cannabis use has
been documented. Most studies have focused on short-term outcomes, however, and
the long-term effects of cannabis use are unclear (Mushtaq et al. 2008). A review by
Mushtaq and colleagues (2008) suggests that cannabis use in patients with psychosis
may be associated with increased body weight, and these authors concluded that
cannabis use may be one factor contributing to the weight and health-related problems of
this patient group.

Predictors of antipsychotic-induced weight-gain


Research indicates that antipsychotic-induced weight-gain is predicted by higher parental
BMI, patients’ premorbid BMI, the female gender, younger age, and non-smoking status
(Gebhardt et al. 2009). These findings suggest that there is a strong impact of
predispositional factors on weight-gain, beyond treatment factors. Additionally, Gebhardt
et al. (2009) found that the diagnosis of a schizophrenia spectrum disorder was related to
an increased BMI and suggest that this may result from a longer duration of atypical
antipsychotic treatment. Similarly, Saddichha et al. (2008) examined a group of patients
diagnosed with first-episode schizophrenia and found that waist circumference and
weight at baseline, as well as antipsychotic use, were related to greater weight-gain.
When looking at the impact of different medications on weight-gain, olanzapine lead to
greater weight-gain as compared to risperidone and haloperidol (Saddichha et al. 2008).

Biological Mechanisms of Weight-gain

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 8 di 19

The underlying pathomechanism behind weight-gain in response to antipsychotic


treatment remains, for the most part, unclear. The strongest correlate of gains in body
weight discovered so far is the relative receptor affinities of the atypical antipsychotics for
histamine H1 receptors; also important is the ratio of their affinity for serotonin 5-HT2 and
dopamine D2 receptors (Wetterling, 2001).

In the past, some of the adverse effects of atypical antipsychotic treatment have been
associated with the antagonism of monoamine receptors; more recent data, however,
indicate that metabolic effects (e.g. hypertriglyceridemia, impaired glucose/insulin
homeostasis) may not be related to these mechanisms (Houseknecht et al. 2007). New
theories of the mechanisms underlying antipsychotic-associated weight-gain focus on the
effect of antipsychotics on peptide hormonal regulators of metabolic control, including
leptin, ghrelin, and adiponectin. Jin and colleagues (2008) found that the weight-gain
associated with medication was directly related to changes in leptin; there were no added
antipsychotic effects on leptin signaling. However, long-term studies on ghrelin showed
increased levels in patients on atypical antipsychotics that typically produce weight-gain.
Thus, it appears that ghrelin, and possibly other peptide hormones, may be useful
predictors of weight-gain in patients who are receiving antipsychotic treatments (Jin et al.
2008).

Tricyclic antidepressants have been shown to increase appetite and carbohydrate


cravings (Garland et al., 1988). Additionally, decreased energy expenditure may
contribute to weight-gain (Fernstrom et al. 1985; Korner& Aronne 2003). In the case of
lithium carbonate therapy, research has shown an insulin-like effect on carbohydrate
metabolism, altered fat cell metabolism, and depressed thyroid function (Ackerman&
Nolan 1998; Garland et al. 1988).

Psychological and Pharmacological Interventions

There are various pharmacological (e.g. switching medications) and nonpharmalogical


(e.g. diet and exercise) interventions for patients who have gained weight as a result of
psychiatric treatment. It seems that modest short-term weight loss is possible with either
type of intervention. The drug reboxetine (4mg daily for 6 weeks) appears effective for
weight prevention while topiramate (100-200mg daily for 12 weeks) is useful for both
prevention and for established weight-gain (Faulkner& Cohn 2006; Faulkner et al. 2007).
Additional research has shown topiramate to result in substantial weight loss when
combined with valproate or clozapine (Gordon& Price 1999; Dursun& Devarajan 2000,
Afshar 2009).

Sibutramine, an SSRI licensed for weight loss, has demonstrated significant weight
reduction in several double-blind placebo-controlled trials (Apfelbaum et al. 1999, Payer

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Preve... Pagina 9 di 19

et al. 2004). In these studies, patients lost about 5% of their initial weight and maintained
this for at least one year, primarily due to reduced appetite and an increase in energy
expenditure (Apfelbaum et al. 1999,). Similar weight loss effects to sibutramine are seen
with orlistat, which reduces intestinal absorption of fat (Finer et al. 2000). Additionally,
metformin, an anti-diabetic drug, can help reduce the weight-gained in response to
olanzapine, valproate, and risperidone (Morrison et al. 2002, Chen et al. 2008, Arman,
2008).

Modifications to diet and physical activity can also be effective. In particular,


cognitive/behavioral interventions that provide strategies for adhering to diet and
exercise lifestyle modifications have proven to be valuable for weight management
(Weber& Wyne, 2006). They implemented a cognitive/behavioral group intervention
modeled after the Diabetes Prevention Project in a group of patients diagnosed with
schizophrenia or schizoaffective taking atypical antipsychotics. After 16 weeks it was
found that the intervention patients lost more weight (2.9% of body weight) than a
control “treatment as usual” group (0.6% body weight). This intervention group consisted
of weekly sessions which centered on various strategies, such as goal setting,
discussions on barriers to change, and plans to increase physical activity. Participants in
the intervention also had to keep a food and activity journal, which was submitted at each
weekly session (Weber& Wyne, 2006).

Thus, there are interventions strategies available to prevent weight-gain and its
associated health risks in individuals undergoing psychiatric treatment. Both
pharmacological and nonpharmacological strategies show promise in weight reduction.
Overall it seems that the best approach is to use pharmacological interventions in
conjunction with dietary and behavioral modifications (Faulkner, 2007). However, given
the modest effect of these interventions, appraising metabolic risk is a critical first step to
preventing weight-gain in patients starting on antipsychotics or antidepressants.
Additionally, in extreme cases, surgery remains an option when other weight control
methods have failed and obesity-related co-morbidities and mortality become a concern
(Expert panel on the identification, 1998). Further research is required to determine
which methods of intervention show the best long-term effects and what individual
differences influence the type of intervention that will be effective.

Managing Weight-gain in Clinical Practice: Management and


Prevention

The weight-gain that can result from treatment with antipsychotic medication may lead
some individuals to discontinue medication, inhibiting their potential for improved mental
health (Monteleone et al. 2009). For those who do continue with their medication, the
associated weight-gain can lead to numerous other health and psychosocial problems.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 10 di 19

Citrome (Bhuvaneshwar et al. 2009) and Vreeland (2009) report that by monitoring body
weight early in treatment, practitioners would be able to better predict patients who are at
high risk for substantial weight-gain. In this way, excessive weight-gain can be prevented
before it becomes an impediment to the improvement of mental health.

Switching antipsychotic medication is one method to reduce body weight, although this
may not be clinically feasible. Switching from one drug to another is a clinical decision
depending on several factors e.g. tolerance, safety and efficacy of molecules used. Such
decisions are always to be taken in the best interest of the patient depending on the
existent state of knowledge.

Evidence for the effectiveness of adjunctive medication strategies is conflicting; however,


lifestyle therapies and other non-pharmacological interventions have proven successful
in controlled clinical trials (Citrome& Vreeland, 2009). Life style treatment includes
cognitive behavioral and educational psychotherapy, regular physical fitness programs,
preferably supervised, follow-up of dietary regimes, and traditionally accepted long
walks. All these are clubbed under the rubric of non-pharmacologic interventions.

Kerwin (2009) reports on a panel of European experts in the field of schizophrenia who
met to discuss improved treatment monitoring as a means of optimizing patient
management. The panel agreed that weight-gain was one of the core parameters to be
monitored in all patients with schizophrenia and that optimizing treatment requires an
individualized management strategy. Kerwin (2009) highlights the fact that treatment
strategies for individuals with schizophrenia need to be switched from medication-based
to more holistic approaches. This would include a multidisciplinary team that would be
able to address the physical health problems experienced by many individuals with
schizophrenia. Psychiatric and general health care needs to be integrated as much as
possible to optimize outcomes (Wadden et al. 2007). In addition to continued patient-
practitioner contact, long-term use of pharmacotherapy combined with lifestyle
modification (diet, physical activity, and behavioral therapy) appears important for long-
term weight control (Wadden et al. 2007). Three medications for weight loss and
maintenance, sibutramine, orlistat, and rimonabant have proven to result in a weight loss
of 7-10% of initial body weight in one year of treatment (Bray, 2007). By maintaining
communication with primary care physicians and monitoring for weight-gain psychiatrists
can help to maintain the physical health of patients.

Best Way Forward

The best way forward in management and prevention is to be vigilant from the very
beginning. Specific measures are required in the clinical practice of psychopharmacology
to deal with weight-gain and related issues:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 11 di 19

1. Thorough baseline assessment of family history, risk factors, health psychology, life
style and dietary habits.
2. Monitor weight and metabolic parameters closely throughout the course of
treatment.
3. Work with a meaningful multidisciplinary team to target all vulnerable areas.
4. Incorporate behavioral intervention programs.
5. Involve dieticians to monitor nutritional requirement.
6. Avoid polypharmacy as much as possible.
7. Attempt to treat weight-gain with behavioral and pharmacological measures.
8. Treat metabolic conditions, like hyperlipidemia and diabetes.
9. Obtain good control over hypertension.
10. Obtain adequate remission of depressive and negative symptoms.
11. Implement motivational therapy when required.
12. Equip clinics with all necessary resources under one umbrella for feasibility.

Summary and Conclusion

Many patients suffering from mental disorders, when exposed to psychotropic


medications, gain a significant amount of weight; a trend acknowledged as a public
health problem due to its correlation with mortality and increased comorbidity of other
physical disorders. This association requires new paradigms of management of
psychiatric disorders that take into account co-morbid physical disorders. An important
aspect of managing side effects of antipsychotics and antidepressants is to use a
combination of administrative, behavioral and medical approaches to assess and treat all
problems that an individual faces. Obesity represents a burden both to the individual and
to society and requires appropriate attention. If feasible, switching medication may be
one solution. In many cases, weight loss (or weight control) programs will need to be
incorporated into an individual holistic treatment plan.

Take home message


In sum, medication-induced weight-gain can be detrimental to a patient’s physical health
and recovery process. To address this issue, a holistic, multidisciplinary approach to
treatment is recommended. It is critical that clinicians take precautions to monitor and
control weight-gain and to treat all problems facing a patient; the best way forward in
management and prevention is to be vigilant from the very beginning.

Conflict of interest
None declared

Author contributions
The first author was responsible for the literature review and the second author was

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 12 di 19

responsible for writing the article.

Declaration
This manuscript is an original, unpublished piece. It has not been submitted for
publication elsewhere.

Questions that this Paper Raises

1. What are the mechanisms through which psychiatric medications cause weight-
gain? Can this information be used to prevent treatment-induced weight-gain?
2. Which pharmacological and nonpharmacological interventions for patients who
have gained weight produce the most weight loss and, more importantly, the best
maintenance of weight lost over the long term?
3. Which cognitive-behavioral intervention strategies (e.g. goal setting, food journals)
are most effective and feasible for individuals diagnosed with schizophrenia,
affective disorders?
4. What are some practical and cost-effective strategies to incorporating a holistic,
multidisciplinary approach to the management of every individual treated with
psychiatric medications?
5. What are the effects of combining weight loss drugs with antipsychotic medications?

About the Author

Amresh Shrivastava, MD, DPM, MRCPsych, is currently an Assistant Professor


of Psychiatry at the University of Western Ontario in London, Ontario, Canada and an
Associate Scientist at the Lawson Health Research Institute. His clinical work involves
early psychosis and acute psychiatric work, and he is the Physician Team Leader for the
Elgin Prevention and Early Psychosis Program (PEPP), Regional Mental Health Care –
St. Thomas, Ontario, Canada. Dr. Shrivstava has also been the Executive Director of
PRERANA Charitable Trust in Mumbai, India since 1992.

Megan Johnston, MA, is currently a PhD Candidate in Psychology at the


University of Toronto in Toronto, Ontario, Canada. Her primary research interests involve
parental and socialization influences on moral development and antisocial and pro-social
behavior in adolescence. She is also affiliated with Regional Mental Health Care – St.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 13 di 19

Thomas, Ontario, Canada where her research focuses on the social and clinical
outcomes of schizophrenia and suicide risk assessment and prevention.

CITATION: Shrivastava A., Johnston M., (2010), Weight-Gain in Psychiatric Treatment: Risks, Implications, and
Strategies for Prevention and Management. In: Psychopharmacology Today: Some Issues (A.R. Singh and S.A. Singh
eds.), MSM, 8, Jan - Dec 2010, p53-68.

References

1. Ackerman S, Nolan L.J. Bodyweight-gain induced by psychotropic drugs: incidence, mechanisms, and
management. CNS Drugs. 1998;9(2):p135–151.

2. Afshar H, Roohafza H, Mousavi G, Golchin S, Toghianifar N, Sadeghi M, Talaei M. Topiramate add-on


treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial. J Psychopharmacol.
2009;23(2):p157–162.

3. Amiel J.M, Mangurian C.V, Ganguli R, Newcomer J.W. Addressing cardiometabolic risk during treatment with
antipsychotic medications. Curr Opin Psychiatry. 2008;21(6):p613–618.

4. Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E. Long-term maintenance of weight


loss after a very-low-calorie diet: A randomized blinded trial of the efficacy and tolerability of sibutramine. Am J
Med. 1999;106(2):p179–184.

5. Allison D.B, Loebel A.D, Lombardo I, Romano S.J, Siu C.O. Understanding the relationship between
baseline BMI and subsequent weight change in antipsychotic trials: Effect modification or regression to the
mean? Psychiatry Res. 2009;170(3):p172–176.

6. Arman S, Sadramely M.R, Nadi M, Koleini N. A randomized, double-blind, placebo-controlled trial of


metformin treatment for weight-gain associated with initiation of risperidone in children and adolescents. Saudi
Med J. 2008;29(8):p1130–1134.

7. Astrup A, Toubro S, Cannon S, Hein P, Madsen J. Thermogenic synergism between ephedrine and caffeine
in healthy volunteers: a double-blind, placebo-controlled study. Metabolism. 1991;40(3):p323–329.

8. Bean M.K, Stewart K, Olbrisch M.E. Obesity in America: Implications for clinical and health psychologists. J
Clin Psychol in Medical Settings. 2008;15(3):p214–224.

9. Bergen D.C, Ristanovic R.K, Waicosky K, Kanner A, Hoeppner T.J. Weight loss in patients taking felbamate.
Clin Neuropharmacology. 1995;18(1):p23–27.

10. Bhuvaneswar C.G, Baldessarini R.J, Harsh V.L, Alpert J.E. Adverse endocrine and metabolic effects of
psychotropic drugs: selective clinical review. CNS Drugs. 2009;23(12):p1003–1021.

11. Boney C.M, Verma A, Tucker R, Vohr B.R. Metabolic syndrome in childhood: associations with birth weight,
maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115(3):p290–296.

12. Bray G.A. Drug treatment of the overweight patient. Gastroenterology. 2007;132(6):p2239–2252.

13. Brost B.C, Goldenberg R.L, Mercer B.M, Iams J.D, Meis P.J, Moawad A.H, et al. The preterm prediction

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 14 di 19

study: association of cesarean delivery with increases in maternal weight and body mass index. Am J Obstet
Gynecol. 1997;177(2):p333–337.

14. Centorrino F, Wurtman J.J, Duca K.A, Fellman V.H, Fogarty K.V, Berry J.M, et al. Weight loss in overweight
patients maintained on atypical antipsychotic agents. Int J Obes. 2006;30(6):p1011–1016.

15. Chen C.H, Chiu C.C, Huang M.C, Wu T.H, Liu H.C, Lu M.L. Metformin for metabolic dysregulation in
schizophrenic patients treated with olanzapine. Prog Neuro-psychopharmacol Biol Psychiatry. 2008;32(4):p925–
931.

16. Citrome L, Vreeland B. Obesity and mental illness. Mod Trends Pharmacopsychiatry. 2009;26:p25–46.

17. Correll C.U, Manu P, Olshanskiy V, Napolitano B, Kane J.M, Malhotra Cardiometabolic risk of second-
generation antipsychotic medications during first-time use in children and adolescents. J Am Med Assoc.
2009;302(16):p1765–1773.

18. Dursun S.M, Devarajan S. Clozapine weight-gain, plus topiramate weight loss. Can J Psychiatry.
2000;45:p198.

19. Fagiolini A, Frank E, Houck P.R, Mallinger A.G, Swartz H.A, Buysse D.J, et al. Prevalence of obesity and
weight change during treatment in patients with bipolar I disorder. J Clin Psychiatry. 2002;63(6):p528–33.

20. Faulkner G, Cohn T.A. Pharmacologic and nonpharmacologic strategies for weight-gain and metabolic
disturbance in patients treated with antipsychotic medications. Can J Psychiatry. 2006;51(8):p502–511.

21. Faulkner G, Cohn T, Remington G. Interventions to reduce weight-gain in schizophrenia. Schizophr Bull.
2007;33(3):p654–656.

22. Fava M. Weight-gain and antidepressants. J Clin Psychiatry. 2000;61(Suppl 11):p37–41.

23. Fernstrom M, Epstein L.H, Spiker D.G, Kupfer D.J. Resting metabolic rate is reduced in patients treated
with antidepressants. Biol Psychiatry. 1985;20(6):p688–692.

24. Finer N, James W.P, Kopelman P.G, Lean M.E, Williams G. One-year treatment of obesity: A randomized,
double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat
Metab Disord. 2000;24:p306–313.

25. Floris M, Lejeune J, Deberdt W. Effect of amantadine on weight-gain during olanzapine treatment. Eur
Neuropsychopharmacol. 2001;11(2):p181–182.

26. Garland E.J, Remick R.A, Zis A.P. Weight-gain with antidepressants and lithium. J Clin Psychopharmacol.
1988;8(5):p323–330.

27. Gebhardt S, Haberhausen M, Heinzel-Gutenbrunner M, Gebhardt N, Remschmidt H, Krieg J.C, et al.


Antipsychotic-induced body weight-gain: predictors and a systematic categorization of the long-term weight
course. J Psychiatr Res. 2009;43(6):p620–626.

28. Goeree R, Farahati F, Burke N, Blackhouse G, O’Reilly D, Pyne J. The economic burden of schizophrenia
in Canada in 2004. Curr Med Res Opin. 2005;21(12):p2017–2028.

29. Gordon A, Price L.H. Mood stabilization and weight loss with topiramate. Am J Psychiatry. 1999;156
(6):p968–968.

30. Gustafson D. A life course of adiposity and dementia. Eur J Pharmacol. 2008;6(1):p163–175.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 15 di 19

31. Haddad P. Weight change with atypical antipsychotics in the treatment of schizophrenia. J
Psychopharmacol. 2005;19(6 Suppl):p16–27.

32. Hebebrand M.D, Hinney A. Environmental and genetic risk factors in obesity. Child Adolesc Psychiatr Clin
N Am. 2009;18(1):p83–94.

33. Houseknecht K.L, Robertson A.S, Zavadoski W, Gibbs E.M, Johnson D.E, Rollema H. Acute effects of
atypical antipsychotics on whole body insulin resistance in rats: implications for adverse metabolic effects.
Neuropsychopharmacology. 2007;32:p289–297.

34. Howard L.M. Fertility and pregnancy in women with psychotic disorders. Eur J Obstet Gynecol Reprod Biol.
2005;119(1):p3–10.

35. Jelalian E, Wember Y.M, Bungeroth H, Birmaher V. Practitioner review: Bridging the gap between research
and clinical practice in pediatric obesity. J Child Psychol Psychiatry. 2007;48(2):p115–127.

36. Jin H, Meyer J.M, Mudaliar S, Jeste D.V. Impact of atypical antipsychotic therapy on leptin, ghrelin, and
adiponecti. Schizophr Res. 2008;100(1-3):p70–85.

37. Kerwin R. Connecting patient needs with treatment management. Acta Psychiatr Scand. 2009;119(Suppl
438):p33–39.

38. Korner J, Aronne L.J. The emerging science of body weight regulation and its impact on obesity treatment.
J Clin Invest. 2003;111(5):p565–570.

39. Kristensen J, Vestergaard M, Wisborg K, Kesmodel U, Secher N.J. Pre-pregnancy weight and the risk of
stillbirth and neonatal death. Br J Obstet Gynaecol. 2005;112:p403–408.

40. Livingstone C, Rampes H. Lithium: a review of its metabolic adverse effects. J Psychopharmacology.
2006;20(3):p347–355.

41. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S, Diav-Citrin O, et al. Pregnancy outcome of women
using atypical antipsychotic drugs: A prospective comparative study. J Clin Psychiatry. 2005;66(4):p444–449.

42. Michelson J, Bancroft S, Targum S, Yongman K, Tepner R. Female sexual dysfunction associated with
antidepressant administration: a randomized, placebo-controlled study of pharmacologic intervention. Am J
Psychiatry. 2000;157(2):p239–243.

43. Moller H.J. Outcomes in major depressive disorder: The evolving concept of remission and its implications
for treatment. World J Biol Psychiatry. 2008;9(2):p102–114.

44. Monteleone P, Martiadis V, Maj M. Management of schizophrenia with obesity, metabolic, and
endocrinological disorders. Psychiatr Clin North Am. 2009;32(4):p775–794.

45. Morrison J.A, Cottingham E.M, Barton B.A. Metformin for weight loss in pediatric patients taking
psychotropic drugs. Am J Psychiatry. 2002;159(4):p655–657.

46. Morrato EH, Newcomer JW, Kamat S, Baser O, Harnett J, Cuffel B, Newcomer JW. Metabolic screening
after the American Diabetes Association’s consensus statement on antipsychotic drugs and diabetes. Diabetes
Care. 2009;32(6):p1037–1042. Epub 2009 Feb 24.

47. Mushtaq F, Mondelli V, Pariante C.M. The metabolic implications of long term cannabis use in patients with
psychosis. Epidemiol Psychiatr Soc. 2008;17(3):p221–226.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 16 di 19

48. Newcomer J.W. Metabolic considerations in the use of antipsychotic medications: A review of recent
evidence. J Clin Psychiatry. 2007;68(Suppl 1):p20–27.

49. Payer J, Hainer V, Ondrejka P, Kajtor Z. Sibutramin in obesity treatment (multi-center, open, prospective 12-
month-long study)] Vnitr Lek. 2004;50(11):p825–829.

50. Saddichha S, Ameen S, Akhtar S. Predictors of antipsychotic-induced weightgain in first-episode psychosis:


conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and
haloperidol. J Clin Psychopharmacol. 2008;28(1):p27–31.

51. Shi H, Clegg D.J. Sex differences in the regulation of body weight. Physiol Behav. 2009;97(2):p199–204.

52. Silverstone T, Smith G, Goodall E. Prevalence of obesity in patients receiving depot antipsychotics. Br J
Psychiatry. 1988;153:p214–217.

53. Simon V, van Winkel R, De Hert M. Are weight-gain and metabolic side effects of atypical antipsychotics
dose dependent? A literature review. J Clin Psychiatry. 2009;70(7):p1041–50.

54. Tarricone I, Ferrari Gozzi B, Serretti A, Grieco D, Berardi D. Weight-gain in antipsychotic-naive patients: a
review and meta-analysis. Psychol Med. 2009;6:p1–14.

55. Umbricht D.S, Pollack S, Kane J.M. Clozapine and weight-gain. J Clin Psychiatry. 1994;55(Suppl B):p157–
60.

56. Vestergaard P, Amidson A, Schou M. linically significant side effects of lithium treatment. Acta Psychiatr
Scand. 1980;62(3):p193–200.

57. Wadden T.A, Butryn M.L, Wilson C. Lifestyle modification for the management of obesity. Gastroenterology.
2007;132(6):p2226–2238.

58. Weber M, Wyne K. A cognitive/behavioral group intervention for weight loss in patients treated with atypical
antipsychotic. Schizophr Res. 2006;83(1):p95–101.

59. Wetterling T. Bodyweight-gain with atypical antipsychotics: A comparative review. Drug Saf. 2001;24(1):p59–
73.

60. Zimmermann U, Rechlin T, Plaskacewicz G, Barocka A, Wildt L, Kaschka W. Effect of naltrexone on weight-
gain and food craving induced by tricyclic antidepressants and lithium: An open study. Bio Psychiatry. 1997;41
(6):p747–749.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 17 di 19

Figures and Tables

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 18 di 19

Table 1
Efficacy of weight control with medication

Medication Efficacy Study


Ephedrine Body weight reduction of 24kg in 24 weeks Astrup et al. 1991
Sibutramine Loss of 5% of initial weight in 24 weeks Apfelbaum et al. 1999
Orlistat Loss of 5% of initial weight in 24 weeks Finer et al. 2000
Topiramate Weight reducing effect in combination with clozapine Dursun & Devarajan, 2000
Metformin Helpful in reversing weight-gain in pediatric patients Morrison et al. 2002
Naltrexone Reduction in food craving; reversal or control of weight-gain Zimmermann et al. 1997
Amantadine Weight loss of 3.5kg in 3-6 months Floris et al. 2001

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011
Weight-Gain in Psychiatric Treatment: Risks, Implications, and Strategies for Pre... Pagina 19 di 19

Figure 1
Causes and effects of weight-gain in psychiatric treatment

Articles from Mens Sana Monographs are provided here courtesy of


Medknow Publications

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/?report=printable 12/05/2011